The central hypothesis of this research is that emphysema is a disease produced by the enzymatic degradation of lung connective tissue, notably lung elastin. The primary source of the enzymes is the circulating neutrophil which contains potent elastases. This research will demonstrate the flux and fate of neutrophils and neutrophil elastase in the normal lung and in the lung of experimental animals which have been subject to chemical, bacterial, enzymatic and environmental (cigarette smoke) exposure to test the effects of these events on the ingress and egress of neutrophils and the effects of elastase on lung elastin. In addition, the role and mechanisms of action of various inhibitors such as the circulating antiprotease, alpha-1 antitrypsin, and inhibitors in bronchial secretions will be investigated for their role in preventing potential emphysematous lung destruction. Enzyme-lung substrate relationship will be investigated with respect to specificity and environmental circumstances promoting in vivo degradation. The effect of these enzymes on tropoelastin will also be investigated. The earliest physiologic abnormalities which may occur in experimental and human emphysema will be investigated with emphasis on the measurement of collateral flow resistance. Finally, resected lungs from humans will be studied after in vivo labeling to determine the effects of cigarette smoke and the presence of emphysema on neutrophil kinetics in the lung.